DESCRIPTION

Each mL contains, in a sterile solution, 10 mg edrophonium chloride compounded with 0.45% phenol as a preservative, and 0.2% sodium sulfite as an antioxidant, buffered with sodium citrate and citric acid, and pH adjusted to approximately 5.4. Structural formula as follows:

Enlon (edrophonium injection) ® is intended for IV and IM use.

For Consumers

What are the possible side effects of edrophonium (Enlon, Tensilon)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

INDICATIONS

Enlon (edrophonium injection) ® is recommended for the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises. Because of its brief duration of action, it is not recommended for maintenance therapy in myasthenia gravis.

Enlon (edrophonium injection) ® is also useful whenever a curareantagonist is needed to reverse the neuromuscular block produced by curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine. It is not effective against decamethonium bromide and succinylcholine chloride. It may be used adjunctively in the treatment of respiratorydepression caused by curare overdosage.

DOSAGE AND ADMINISTRATION

Intravenous Dosage (Adults): A tuberculinsyringe containing 1 mL (10 mg) of Enlon (edrophonium injection) ® is prepared with an intravenous needle, and 0.2 mL (2 mg) is injected intravenously within 15 to 30 seconds. The needle is left in situ. Only if no reaction occurs after 45 seconds is the remaining 0.8 mL (8 mg) injected. If a cholinergic reaction (muscarinic side effects, skeletal muscle fasciculations and increased muscle weakness) occurs after injection of 0.2 mL (2 mg), the test is discontinued and atropine sulfate, 0.4 mg to 0.5 mg, is administered intravenously. After one-half hour the test may be repeated.

Dosage (Children): The intravenous testing dose of Enlon (edrophonium injection) ® in children weighing up to 75 lbs is 0.1 mL (1 mg); above this weight, the dose is 0.2 mL (2 mg). If there is no response after 45 seconds, it may be titrated up to 0.5 mL (5 mg) in children under 75 lbs, given in increments of 0.1 mL (1 mg) every 30 to 45 seconds and up to 1 mL (10 mg) in heavier children. In infants, the recommended dose is 0.05 mL (0.5 mg). Because of technical difficulty with intravenous injection in children, the intramuscular route may be used. In children weighing up to 75 lbs, 0.2 mL (2 mg) is injected intramuscularly, in children weighing more than 75 lbs, 0.5 mL (5 mg) is injected intramuscularly. All signs which would appear with the intravenous test appears with the intramuscular test except that there is a delay of two to ten minutes before a reaction is noted.

Enlon (edrophonium injection) ® Test for Evaluation of Treatment Requirements in Myasthenia Gravis: The recommended dose is 0.1 mL to 0.2 mL (1 mg to 2 mg) of Enlon (edrophonium injection) ®, administered intravenously one hour after oral intake of the drug being used in treatment. 1-5 Response will be myasthenic in the undertreated patient, adequate in the controlled patient, and cholinergic in the overtreated patient. Responses to Enlon (edrophonium injection) ® in myasthenic and nonmyasthenic individuals are summarized in the following chart.

* Myasthenic Response- occurs in untreated myasthenics and may serve to establish diagnosis; in patients under treatment, indicates that therapy is inadequate.

¬ Adequate Response- observed in treated patients when therapy is stabilized: a typical response in normal individuals. In addition to this response in non-myasthenics, the phenomenon of forced lid closure is often observed in psychoneurotics.

¬° Cholinergic Response- seen in myasthenics who have been overtreated with anticholinesterase drugs.

Enlon (edrophonium injection) ® Test in Crisis: The term crisis is applied to the myasthenic whenever severe respiratory distress with objective ventilatory inadequacy occurs and the response to medication is not predictable. This state may be secondary to a sudden increase in severity of myasthenia gravis (myasthenic crisis), or to overtreatment with anticholinesterase drugs (cholinergic crisis).

When a patient is apneic, controlled ventilation must be secured immediately in order to avoid cardiac arrest and irreversible central nervous system damage. No attempt is made to test with Enlon (edrophonium injection) ® until respiratory exchange is adequate.

Dosage used at this time is most important: If the patient is cholinergic, Enlon (edrophonium injection) ® will cause increased or opharyngeal secretions and further weakness in the muscles of respiration. If the crisis is myasthenic, the test clearly improves respiration and the patient can be treated with longer-acting intravenous anticholinesterase medication. When the test is performed, there should not be more than 0.2 mL (2 mg) Enlon (edrophonium injection) ® in the syringe. An intravenous dose of 0.1 mL (1 mg) is given initially. The patient†s heart action is carefully observed. If, after an interval of one minute, this dose does not further impair the patient, the remaining 0.1 mL (1 mg) can be injected. If no clear improvement of respiration occurs after 0.2 mL (2 mg) dose, it is usually wisest to discontinue all anticholinesterase drug therapy and secure controlled ventilation by tracheostomy with assisted respiration. 5

For Use as a Curare Antagonist: Enlon (edrophonium injection) ® should be administered by intravenous injection in 1 mL (10 mg) doses given slowly over a period of 30 to 45 seconds so that the onset of cholinergic reaction can be detected. This dosage may be repeated whenever necessary. The maximal dose for any one patient should be 4 mL (40 mg). Because of its brief effect, Enlon (edrophonium injection) ® should not be given prior to the administration of curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine: it should be used at the time when its effect is needed. When given to counteract curare overdosage, the effect of each dose on the respiration should be carefully observed before it is repeated, and assisted ventilation should always be employed.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

SIDE EFFECTS

Careful observation should be made for severe cholinergic reactions in the hyperreactive individual. The myasthenic patient in crisis who is being tested with Enlon (edrophonium injection) ® should be observed for bradycardia or cardiac standstill and cholinergic reactions if an overdose is given.

The following reactions common to anticholinesterase agents may occur, although not all of these reactions have been reported with the administration of Enlon (edrophonium injection) ®, probably because of its short duration of action and limited indications:

DRUG INTERACTIONS

Care should be given when administering this drug to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. Since symptoms of anticholinesterase overdose (cholinergic crisis) may mimic underdosage (myasthenic weakness), their condition may be worsened by the use of this drug. (See OVERDOSAGE section for treatment.)

WARNINGS

Whenever anticholinesterase drugs are used for testing, a syringe containing 1 mg of atropine sulfate should be immediately available to be given in aliquots intravenously to counteract severe cholinergic reactions which may occur in the hypersensitive individual, whether he is normal or myasthenic. Enlon (edrophonium injection) ® should be used with caution in patients with bronchial asthma or cardiac dysrhythmias. The transient bradycardia which sometimes occurs can be relieved by atropine sulfate. Isolated instances of cardiac and respiratory arrest following administration of Enlon (edrophonium injection) ® have been reported. It is postulated that these are vagotonic effects.

Contains sodium sulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Usage in Pregnancy: The safety of Enlon (edrophonium injection) ® during pregnancy or lactation in humans has not been established. Therefore, use of Enlon (edrophonium injection) ® in women who may become pregnant requires weighing the drug†s potential benefits against its possible hazards to mother and child.

PRECAUTIONS

Patients may develop †anticholinesterase insensitivity¬Ě for brief or prolonged periods. During these periods the patients should be carefully monitored and may need respiratory assistance. Dosages of anticholinesterase drugs should be reduced or withheld until patients again become sensitive to them.

OVERDOSE

With drugs of this type, muscarine-like symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions and bradycardia) often appear with overdosage (cholinergic crisis). An important complication that can arise is obstruction of the airway by bronchial secretions. These may be managed with suction (especially if tracheostomy has been performed) and by the use of atropine. Many experts have advocated a wide range of dosages of atropine (for Enlon (edrophonium injection) ®, see atropine dosage below), but if there are copious secretions, up to 1.2 mg intravenously may be given initially and repeated every 20 minutes until secretions are controlled. Signs of atropine overdosage such as dry mouth, flush and tachycardia should be avoided as tenacious secretions and bronchial plugs may form. A total dose of atropine of 5 to 10 mg or even more may be required. The following steps should be taken in the management of overdosage of Enlon (edrophonium injection) ®:

1. Adequate respiratory exchange should be maintained by assuring an open airway and by the use of assisted respiration augmented by oxygen.

2. Cardiac function should be monitored until complete stabilization has been achieved.

3. Atropine sulfate in doses of 0.4 to 0.5 mg should be administered intravenously. This may be repeated every 3 to 10 minutes. Because of the short duration of action of Enlon (edrophonium injection) ® the total dose required will seldom exceed 2 mg.

4. Pralidoxime chloride (a cholinesterase reactivator) may be given intravenously at the rate of 50 to 100 mg per minute; usually the total dose does not exceed 1000 mg. Extreme caution should be exercised in the use of pralidoxime chloride when the cholinergic symptoms are induced by double-bond phosphorous anticholinesterase drugs.9

5. If convulsions occur or shock is present, appropriate measures should be instituted.

CONTRAINDICATIONS

Known hypersensitivity to anticholinesterase agents; intestinal and urinary obstructions of mechanical type.

CLINICAL PHARMACOLOGY

Enlon (edrophonium injection) ® is an anticholinesterase drug. Its pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes.